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Effects of vesnarinone on cytokine production and activation of murine microglia.

机译:维纳酮对小鼠小胶质细胞因子产生和激活的影响。

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摘要

Tumor necrosis factor alpha (TNF alpha) is considered to play a critical role in the development of various pathological processes in the central nervous system (CNS), such as neuronal degeneration, demyelination and gliosis. In order to search for agents which suppress TNF alpha production in the CNS for future treatment of these pathological conditions, the effects of a synthetic oral inotropic agent, vesnarinone, on murine microglia were examined. Vesnarinone significantly suppressed TNF alpha production by microglia in a dose-dependent manner, without affecting their viability, enzyme activity or expression of the major histocompatibility complex. Since the reported maximum serum concentration is high enough to suppress TNF alpha production in vitro (about 20 microM) after oral administration of the therapeutic dose of vesnarinone, this drug will be useful to treat intractable neurological diseases such as neurodegenerative disorders, multiple sclerosis or HIV-related neurological disorders.
机译:肿瘤坏死因子α(TNF alpha)被认为在中枢神经系统(CNS)的各种病理过程的发展中起关键作用,例如神经元变性,脱髓鞘和神经胶质增生。为了寻找在中枢神经系统中抑制TNFα产生的药物,以进一步治疗这些病理状况,研究了合成的口服正性肌力药物vesnarinone对鼠小胶质细胞的作用。 Vesnarinone以剂量依赖性方式显着抑制小胶质细胞产生的TNFα,而不会影响其生存力,酶活性或主要组织相容性复合物的表达。由于报告的最大血清浓度足够高,可以在口服给予治疗剂量的维那那酮后抑制体外TNFα的产生(约20 microM),因此该药物可用于治疗顽固性神经系统疾病,例如神经退行性疾病,多发性硬化或HIV相关的神经系统疾病。

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